Cleaning and Disinfectant Chemical Exposures and Temporal Associations with COVID-19 - National Poison Data System, United States, January 1, 2020-March 31, 2020.

On January 19, 2020, the state of Washington reported the first U.S. laboratory-confirmed case of coronavirus disease 2019 (COVID-19) caused by infection with SARS-CoV-2 (1). As of April 19, a total of 720,630 COVID-19 cases and 37,202 associated deaths* had been reported to CDC from all 50 states, the District of Columbia, and four U.S. territories (2). CDC recommends, with precautions, the proper cleaning and disinfection of high-touch surfaces to help mitigate the transmission of SARS-CoV-2 (3). To assess whether there might be a possible association between COVID-19 cleaning recommendations from public health agencies and the media and the number of chemical exposures reported to the National Poison Data System (NPDS), CDC and the American Association of Poison Control Centers surveillance team compared the number of exposures reported for the period January-March 2020 with the number of reports during the same 3-month period in 2018 and 2019. Fifty-five poison centers in the United States provide free, 24-hour professional advice and medical management information regarding exposures to poisons, chemicals, drugs, and medications. Call data from poison centers are uploaded in near real-time to NPDS. During January-March 2020, poison centers received 45,550 exposure calls related to cleaners (28,158) and disinfectants (17,392), representing overall increases of 20.4% and 16.4% from January-March 2019 (37,822) and January-March 2018 (39,122), respectively. Although NPDS data do not provide information showing a definite link between exposures and COVID-19 cleaning efforts, there appears to be a clear temporal association with increased use of these products.

Retrospective review of SGLT2 inhibitor exposures reported to 13 poison centers.

BACKGROUND: SGLT2 inhibitors are a new class of oral antidiabetics prescribed in the United States since 2013. They act by inhibiting reabsorption of glucose in the proximal convoluted tubule of the kidney, allowing excess glucose to be excreted. Little has been reported regarding effects of non-therapeutic exposure to this class of medication. METHODS: Retrospective records from 13 poison centers were examined for human exposures to SGLT2 inhibitors between 1st January 2013 and 31st December 2016. Exclusion criteria included multi-substance exposures and exposures without any follow-up call. Data examined included patient age, chronicity of exposure, clinical effects, management site, treatments administered, duration of follow-up, and outcome. RESULTS: Eighty-eight cases met inclusion criteria. Patient age ranged from 1 to 75 years; 49 were evaluated in a health care facility with 18 admissions. No symptoms developed in 80 (91%) patients, 6 (7%) developed minor symptoms, and 2 (2%) developed moderate symptoms. Hypoglycemia was not observed. Mean time to final follow-up was 9.3 h, ranging from 1 to 42 h; median was 6 h. Of the two patients who developed moderate symptoms, one was a 65 year old male who developed metabolic acidosis and hypokalemia while taking canagliflozin therapeutically; the other a 43-year-old female who developed tachycardia and mild hypertension following the intentional ingestion of 6000 mg of canagliflozin. DISCUSSIONS: The number of patients evaluated in a health care facility is most likely reflective of a cautious approach to dealing with a new class of drug. Exposures were generally well-tolerated and managed with minimal intervention. CONCLUSIONS: In this retrospective series, acute ingestions of SGLT2 inhibitors were well-tolerated with no hypoglycemia and only minor effects. For young children with unintentional ingestions, a reasonable approach to home management would include at least one follow-up for signs and symptoms of possible toxicity including mental status changes, polyuria, or tachypnea.

Mercury Poisoning at a Home Day Care Center - Hillsborough County, Florida, 2015.

On November 12, 2015, the Florida Poison Information Center Tampa notified the Florida Department of Health in Hillsborough County of a boy aged 3 years with a urine mercury level of 79 µg/L (normal <10 µg/L). The patient had been admitted to the hospital on October 9, 2015 after a 3-4 week history of anorexia, weight loss, and lethargy. In the hospital, he developed a maculopapular rash, acrodynia (painful, pink discoloration of the hands and feet), tachycardia, hypertension, weakness, sweating, excessive salivation, and altered mental status. Subsequent investigation identified the source of the mercury exposure to be a broken sphygmomanometer (blood pressure monitor) at the home day care center attended by the child.

An Observational Study of the Factor Xa Inhibitors Rivaroxaban and Apixaban as Reported to Eight Poison Centers.

STUDY OBJECTIVE: Rivaroxaban and apixaban are part of a new group of oral anticoagulants targeting factor Xa and approved by the Food and Drug Administration in 2011 and 2012. These oral anticoagulants are administered at fixed daily doses, without the need for laboratory-guided adjustments. There are limited data available on supratherapeutic doses or overdose of the oral Xa inhibitors. This study characterizes the clinical effect in patients exposed to rivaroxaban and apixaban. METHODS: A retrospective study collected data from 8 regional poison centers covering 9 states. Cases were initially identified by a search of the poison centers' databases for case mentions involving a human exposure to Xarelto, rivaroxaban, Eliquis, or apixaban. Inclusion criteria included single-substance exposure. Exclusion criteria were animal exposure, polysubstance exposure, or information call. Data for the study were collected by individual chart review, including case narratives, and compiled into a single data set. RESULTS: There were 223 patients: 124 (56%) were female patients, mean age was 60 years, and 20 were children younger than 12 years (9%). One hundred ninety-eight patients ingested rivaroxaban (89%) and 25 ingested apixaban (11%). Dose was reported in 182 rivaroxaban patients, with a mean dose of 64.5 mg (range 15 to 1,200 mg), and in 21 apixaban patients, with a mean dose of 9.6 mg (range 2.5 to 20 mg). For rivaroxaban, prothrombin time was measured in 49 patients (25%) and elevated in 7; partial thromboplastin time, measured in 49 (25%) and elevated in 5; and international normalized ratio, measured in 61 (31%) and elevated in 13. For apixaban, prothrombin time was measured in 6 patients (24%) and elevated in none; partial thromboplastin time, measure in 6 (24%) and elevated in none; and international normalized ratio, measured in 5 patients (20%) and elevated in none. Bleeding was reported in 15 patients (7%): 11 rivaroxaban and 4 apixaban. The site of bleeding was gastrointestinal (8), oral (2), nose (1), bruising (1), urine (1), and subdural (1). The subdural bleeding occurred after fall and head injury. All cases with bleeding involved long-term ingestions. Coagulation test results were normal in most patients with bleeding: prothrombin time 5 of 6 (83%), partial thromboplastin time 5 of 6 (83%), and international normalized ratio 5 of 9 (55%). Blood products were used in 7 rivaroxaban patients (1 suicide) and 3 apixaban patients. No bleeding or altered coagulation test results occurred in children, which all involved a one-time ingestion. All 12 suicide attempts involved rivaroxaban: altered coagulation test results occurred for 5 patients (42%), no bleeding occurred in any suicide attempt patient, 1 patient was treated with fresh frozen plasma (international normalized ratio 12.47), and dose by patient history did not predict risk of altered coagulation or bleeding. Two rivaroxaban patients experienced elevation of hepatic transaminase levels greater than 1,000 U/L. CONCLUSION: Bleeding after Xa inhibitor ingestion as a single agent is uncommon. Prothrombin time, partial thromboplastin time, or international normalized ratio may be elevated in a minority of cases but appears unreliable to measure risk of bleeding. Massive acute ingestion in suicide attempt may result in significant anticoagulation. Single exploratory ingestion by children was not associated with toxicity.

Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management.

The prevalence of attention-deficit hyperactivity disorder (ADHD) in the USA is estimated at approximately 4-9% in children and 4% in adults. It is estimated that prescriptions for ADHD medications are written for more than 2.7 million children per year. In 2010, US poison centers reported 17,000 human exposures to ADHD medications, with 80% occurring in children <19 years old and 20% in adults. The drugs used for the treatment of ADHD are diverse but can be roughly separated into two groups: the stimulants such as amphetamine, methylphenidate, and modafinil; and the non-stimulants such as atomoxetine, guanfacine, and clonidine. This review focuses on mechanisms of toxicity after overdose with ADHD medications, clinical effects from overdose, and management. Amphetamine, dextroamphetamine, and methylphenidate act as substrates for the cellular monoamine transporter, especially the dopamine transporter (DAT) and less so the norepinephrine (NET) and serotonin transporter. The mechanism of toxicity is primarily related to excessive extracellular dopamine, norepinephrine, and serotonin. The primary clinical syndrome involves prominent neurological and cardiovascular effects, but secondary complications can involve renal, muscle, pulmonary, and gastrointestinal (GI) effects. In overdose, the patient may present with mydriasis, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and seizures. The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. Modafinil is not US FDA approved for treatment of ADHD; however, it has been shown to improve ADHD signs and symptoms and has been used as an off-label pharmaceutical for this diagnosis in both adults and children. The mechanism of action of modafinil is complex and not fully understood. It is known to cause an increase in extracellular concentrations of dopamine, norepinephrine, and serotonin in the neocortex. Overdose with modafinil is generally of moderate severity, with reported ingestions of doses up to 8 g. The most common neurological effects include increased anxiety, agitation, headache, dizziness, insomnia, tremors, and dystonia. The management of modafinil overdose is largely supportive, with a focus on sedation, and control of dyskinesias and blood pressure. Atomoxetine is a selective presynaptic norepinephrine transporter inhibitor. The clinical presentation after overdose with atomoxetine has generally been mild. The primary effects have been drowsiness, agitation, hyperactivity, GI upset, tremor, hyperreflexia, tachycardia hypertension, and seizure. The management of atomoxetine overdose is largely supportive, with a focus on sedation, and control of dyskinesias and seizures. Clonidine is a synthetic imidazole derivative with both central and peripheral alpha-adrenergic agonist actions. The primary clinical syndrome involves prominent neurological and cardiovascular effects, with the most commonly reported features of depressed sensorium, bradycardia, and hypotension. While clonidine is an anti-hypertensive medication, a paradoxical hypertension may occur early with overdose. The clinical syndrome after overdose of guanfacine may be mixed depending on central or peripheral alpha-adrenoreceptor effects. Initial clinical effects may be drowsiness, lethargy, dry mouth, and diaphoresis. Cardiovascular effects may depend on time post-ingestion and may present as hypotension or hypertension. The management of guanfacine overdose is largely supportive, with a focus on support of blood pressure. Overdose with ADHD medications can produce major morbidity, with many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are rare with appropriate care.

Evaluation of changes in poisoning in young children: 2000 to 2010.

OBJECTIVE: The nature of pediatric poisonings is dynamic, with changes occurring over time. We evaluated poisoning in children younger than 6 years for trends during an 11-year period regarding the substances involved in the poisoning, medical outcomes, and health care use. METHODS: This was retrospective study of poisoning in children younger than 6 years reported to 12 poison centers in 5 U.S. states for the years 2000 through 2010. Data abstracted included substance category involved in the exposure, age of patient, year of occurrence, location of patient management, and medical outcome. RESULTS: There were 2,577,036 poison exposures in children younger than 6 years, with a 12.4% increase from 210,270 poison exposures in 2000 to 236,425 poison exposures in 2010. There was a 33% increase (P < 0.05) in pharmaceutical related exposures in children younger than 6 years and a 2.8% decline in the number of nonpharmaceutical related exposures. Among those substance categories representing more than 1% of exposures, the only pharmaceutical showing decline was cough/cold preparations. There was a 53% increase in serious medical outcomes, including 119 deaths and a significant increase in health care facility use, primarily owing to pharmaceutical exposures. CONCLUSIONS: Poisoning in young children increasingly involves pharmaceuticals and is associated with an increased number of serious outcomes and children treated in a health care facility. We believe that these changes are related to increased availability of medications in the home and poison prevention education efforts should include a focus on the availability of these products to small children.

A 9-state analysis of designer stimulant, "bath salt," hospital visits reported to poison control centers.

STUDY OBJECTIVE: A new generation of designer stimulants marketed as "bath salts" emerged in late 2010. The goal is to describe the epidemiologic emergence of designer stimulants in 9 states in the Midwest. METHODS: A retrospective review of the National Poison Data System was performed between November 1, 2010, and November 30, 2011. Inclusion criteria were health care-evaluated bath salts or other synthetic stimulants exposures. Cases were excluded if the exposure was unrelated to a designer stimulant. Demographic and clinical characteristics of cases were calculated and differences in outcome and exposure by generation were examined. RESULTS: One thousand six hundred thirty-three patients met the inclusion criteria. Age ranged from 1 day to 61 years (mean=29.2 years), with 67.9% male patients. The most common clinical features were agitation (62.2%), tachycardia (55.2%), and hallucinations (32.7%). In addition to 15.5% of patients having a major medical effect, 0.6% died. Reason for use was primarily intentional abuse (88.5%). However, 0.7% of patients reported withdrawal. Treatment involved primarily benzodiazepines (58.5%), with 8.7% of patients being intubated. Baby Boomers were more likely to have a major medical outcome (24.2%) and to report injection as the method of administration (8.6%-12.9%). CONCLUSION: Synthetic stimulants rapidly swept across the Midwest, resulting in more than 1,600 patients seeking medical care. Serious medical effects or death was observed in 16.1% of cases. Older generations were more likely to inject and to have a major medical outcome.

Diphenhydramine dose-response: a novel approach to determine triage thresholds.

CONTEXT: It is unclear how much diphenhydramine (DPH) is toxic in humans. Previous dose-response studies have had conflicting results. Objective. We sought to evaluate DPH dose-response using a unique method that utilizes acetaminophen (APAP) serum concentrations to estimate DPH doses in patients ingesting APAP/DPH in a fixed-combination product. METHODS: We retrospectively analyzed APAP/DPH-only exposures in patients 2-80 years of age using case data from 15 U.S. poison centers. DPH dose was extrapolated from measured serum APAP concentrations. A clinically significant response (CSR) was predefined in terms of eight specific manifestations (e.g., coma) that would warrant emergency department intervention. Nominal logistic regression was used to model the probability of each recorded manifestation across DPH dose ranges examining fits for mg, mg/kg, log10 mg, and log10 mg/kg DPH doses. The threshold value where patients reliably became symptomatic was determined by further examining receiver operating characteristic curves. RESULTS: There were 509 cases that met inclusion criteria. Forty-five patients (9%) developed CSRs. A higher percentage of patients developed CSR at ≥ 7.5 mg/kg DPH and ≥1 g total DPH cutoff points (p < 0.05, Fisher's exact test). The best model for predicting the probability of CSR was a logistic fit of log(10) mg/kg dose (p < 0.05). By this model, for every 1 log(10) unit increase of mg/kg DPH dose, the odds of developing a CSR increased 47-fold (95% CI 17, 154). Receiver operating characteristic analyses showed a dose-related progression of symptoms. The cut-point with greatest sensitivity (98%) versus 1-specificity (57%) corresponded to an extrapolated mg/kg DPH dose of 8.2 mg/kg (95% CI 5.6, 10.5). CONCLUSION: Our findings support the current American Association of Poison Control Centers' guideline recommendation to refer patients to the hospital for evaluation if they have ingested greater than or equal to 7.5 mg/kg of DPH.

Unintentional child poisonings through ingestion of conventional and novel tobacco products.

OBJECTIVE: This study examines child poisonings resulting from ingestion of tobacco products throughout the nation and assesses the potential toxicity of novel smokeless tobacco products, which are of concern with their discreet form, candy-like appearance, and added flavorings that may be attractive to young children. METHODS: Data representing all single-substance, accidental poisonings resulting from ingestion of tobacco products by children <6 years of age, reported to poison control centers, were examined. Age association with ingestion of smokeless tobacco versus other tobacco products was tested through logistic regression. Total nicotine content, pH, and un-ionized nicotine level were determined, and the latter was compared with values for moist snuff and cigarettes. RESULTS: A total of 13,705 tobacco product ingestion cases were reported, >70% of which involved infants <1 year of age. Smokeless tobacco products were the second most common tobacco products ingested by children, after cigarettes, and represented an increasing proportion of tobacco ingestions with each year of age from 0 to 5 years (odds ratio: 1.94 [95% confidence interval: 1.86-2.03]). A novel, dissolvable, smokeless tobacco product with discreet form, candy-like appearance, and added flavorings was found to contain an average of 0.83 mg of nicotine per pellet, with an average pH of 7.9, which resulted in an average of 42% of the nicotine in the un-ionized form. CONCLUSION: In light of the novelty and potential harm of dissolvable nicotine products, public health authorities are advised to study these products to determine the appropriate regulatory approach.

Effect of scheduling tramadol as a controlled substance on poison center exposures to tramadol.

BACKGROUND: There is limited information on the effect of scheduling a drug as a controlled substance with comparable data from both a pre-scheduling and post-scheduling time period. OBJECTIVE: To investigate the temporal changes on poisoning cases involving tramadol in 4 states: 2 states where it has been scheduled and 2 where it is not scheduled. METHODS: Databases were searched for all cases involving tramadol reported from 2003 through 2009 at 6 regional poison centers that served Arkansas, Kentucky, Ohio, and West Virginia. To allow for comparison based on population, state population estimates were obtained from the US Census Bureau. RESULTS: Over the 7-year study period, the number of tramadol cases increased from 401 per year to 1009 cases per year. The mean annual increase in tramadol cases for all 4 states ranged from 8.8% to 14.1%. Post-scheduling in Arkansas and Kentucky, there was a mean decrease in cases of 4% and 31%, respectively. During this same period, the comparison states of West Virginia and Ohio showed a continued increase of 14% and 23%, respectively. The mean annual increase in tramadol cases per 100,000 population for all 4 states ranged from 16% to 31%. Post-scheduling of tramadol, there was an annual decrease in tramadol human exposures of 5% to 31% in Arkansas and Kentucky, respectively. During this same period, West Virginia and Ohio showed a continued annual increase of 14%. CONCLUSIONS: The decrease in the number of cases of tramadol exposure following its addition to the schedule of controlled substances in Kentucky and Arkansas suggests that adding a drug to the schedule of controlled substances may result in a decrease in poisoning exposures related to that drug.

Toxicity from modafinil ingestion.

INTRODUCTION: Modafanil, a non-amphetamine stimulant, is used for narcolepsy, sleep apnea, and shift work sleep disorder. There is little available information on the toxicity of modafinil overdose. METHOD: We performed a retrospective multi-poison center chart review of patients from 11 states who had a single substance ingestion of modafanil with follow up to a known outcome for the years 2000-2007. Data collected included age, gender, dose ingested, clinical effects, length of hospital stay, and medical outcome. RESULTS: There were 137 patients, of whom 85 (63%) were female. Ages ranged from 1 to 82 years with a mean and median of 22 years (+18) and 20 years, respectively, with 43 patients (31%) aged <6 years. Most frequently reported clinical effects were tachycardia (n = 38), insomnia (n = 33), agitation (n = 27), dizziness (n = 25), and anxiety (n = 24). Forty-five patients were managed at home and 92 in a health-care setting, with only 23 (17%) requiring a medical admission. Therapies included benzodiazepines (n = 14), diphenhydramine (n = 5), beta-blockers (n = 3), haloperidol (n = 2), IV fluid hydration (n = 2), and one each of nitroglycerin, epinephrine, benztropine, and promethazine. CONCLUSIONS: In this case series, clinical effects of modafinil overdoses were generally mild with predominantly tachycardia and CNS toxicity. However, clinically significant effects warranting specific therapy occurred in a minority of patients.